Center for Quantitative Electrocardiography and Cardiac Safety

描述(由申请人提供)： 心脏安全仍然是一个主要的公共卫生问题。例如，心脏病猝死(SCD)占所有心脏病死亡人数的一半，是美国最大的自然死亡原因(每年约有325,000名成年人死亡)。尽管努力通过早期高级护理来减少这一数字，但显然需要改进风险分层技术，以优化植入式除颤器和药物疗法等预防疗法的使用。与此同时，心脏安全也是新分子实体开发中最具挑战性的障碍之一。据估计，在药物开发中测试的所有药物中，多达86%的药物显示出钾离子动力学的特异性抑制活性，在某些情况下，这可能会导致尖端扭矩，并可能导致SCD。根据美国食品和药物管理局(FDA)的说法，当前药物无法有效筛选出潜在有害药物的主要原因是缺乏更好的标记物来提高新化合物的可预测性和有效性。体表心电图(ECG)作为评估药物心脏毒性、预测心律失常事件以及对心脏病和非心脏病患者进行风险分层的一种非侵入性方法具有至关重要的作用。我们向NHLBI建议，通过支持其围绕1)计算机资源(数据存储和计算中心)的开发和维护、2)医疗信息的部署和3)科学网络的形成，来支持“定量心电和心脏安全中心”(CES)的创建。CES将托管遥测和Holter心电仓库，这一倡议目前由一个工作组实施，该工作组由FDA、罗切斯特大学及其医学中心的工作人员组成。CES将把这些资源分发给国际科学界，分享独特的临床和心电信息，用于设计和验证提高定量心电图仪和心脏安全性的技术。

DESCRIPTION (provided by applicant): Cardiac safety remains a major public health concern. Sudden cardiac death (SCD) for instance, is responsible for half of all heart disease deaths and is the largest cause of natural death in the U.S. (representing about 325,000 adults each year). Despite the effort implemented to reduce this number by early advanced care, there is a clear need for the improvement of risk stratification techniques to optimize the use of prophylactic therapies such as implantable defibrillators and drug therapies. Meanwhile cardiac safety is also one of the most challenging hurdles in the development of new molecular entities. It has been estimated that as many as 86% of all drugs tested in pharmaceutical development show specific inhibitory activity of potassium ion kinetics which in some cases can lead to torsades de pointes and potentially to SCD. According to the US Food and Drug Administration (FDA), the main reason for the inability of the current pharmaceutical to effectively screen out potentially harmful drugs is the lack of better markers to improve predictability and efficacy of new compounds. The roles of the surface electrocardiograms (ECGs) as a noninvasive approach to assess drug cardiotoxicity, to predict arrhythmic events, and to risk stratify cardiac and non-cardiac patients represent a matter of paramount importance. We propose to the NHLBI to enable the creation of a "Center for Quantitative Electrocardiography and Cardiac Safety" (CES) by supporting its inceptive activities around 1) the development and maintenance of computer resources (data storage and computing center), 2) the deployment of medical information and 3) the formation of a scientific network. The CES will host the Telemetric and Holter ECG Warehouse, an initiative currently implemented by a working group consisting of staff members from the FDA, the University of Rochester and its Medical Center. The CES will distribute these resources to the International scientific community, sharing unique clinical and ECG information for the design and validation of technologies to improve quantitative electrocardiography and cardiac safety.